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Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes.

ABSTRACT: This superseries contain NanoString GeoMx spatial profiling datasets that measured RNA and protein expression levels from ROIs of mice that received fear-conditioning and/or sleep deprivation. ROIs were collected from both hemispheres of the brain, including 5 different subregions of the hippocampus (CA1, CA3, DG-superior blade, DG-inferior blade, and DG-hilus).

ORGANISM(S): Mus musculus blank sample

PROVIDER: GSE229082 | GEO | 2024/02/27

REPOSITORIES: GEO

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Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes [spatial protein expression level]

Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.

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Engram-specific transcriptome profiling of contextual memory consolidation

Project description:Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.

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Project description:To assess whether transcriptional differences exist in the epithelial tissue and the inflammatory infiltrate of invasive Aspergillus tracheobronchitis in patients with severe influenza or severe COVID-19, we performed GeoMx spatial transcriptomics on four biopsy samples in total: two of patients with influenza-associated pulmonary aspergillosis (IAPA) and two of patients with COVID-19-associated pulmonary aspergillosis (CAPA). Several regions of interest (ROIs) were delineated in each biopsy sample, and transcriptomic data was derived of each of these ROIs using GeoMx with a whole transcriptome atlas with SARS-CoV-2 spike-in.

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Project description:Previous studies of age-related transcriptional changes indicate that cognitive impairments are associated with differentially expressed genes DEGs linked to defined neural systems; however, studies that examine multiple regions of the hippocampus fail to find major links between behavior and transcription in the dentate gyrus DG. The DG is implicated in pattern separation PS and exhibits multiple age-related changes that may affect PS performance. We hypothesize that an age-related decline in PS performance is associated with distinct changes in transcriptional profile, most strongly within the DG compared to other hippocampal subregions. We used a water maze beacon discrimination task to characterize PS in young 5 mo and middle-age 12 mo male F344 rats, followed by a spatial reference memory test. Middle-age rats showed consistent deficits in discriminating two identical beacons compared to young. Reference memory was not different between these two age groups. Interestingly, with increasing spatial overlap between the cues, older animals appeared to compensate for impaired PS performance though greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions DG, CA1, and CA3 indicated that the DG of middle-age rats expressed more genes correlated with PS performance. In contrast, reliance on a spatial reference memory was associated with differential expression of genes in regions CA1 and CA3. These results indicate that the beacon task is sensitive to PS impairment as early as middle-age, and distinct gene profiles are observed in neural circuits that underlie different strategies used to solve the task.

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Project description:miRNA profiling was carried out using the miRCURY LNA™ microRNA Array (6th gen - hsa, mmu & rno) miRNA were profiled in amygdala brain tissue obtained from adult mice 30 mins after auditory fear conditioning and expression levels compared to tissue obtained from Home cage controls Adult male mice were fear conditioned using tone-shock pairings and brains were harvested 30 mins later. The brains of Home Cage controls and Fear Conditioned animals (n = 4/group) were then punched to collect amygdala tissue. miRNA were extracted using the Qiagen miRNeasy Kit, and then shipped to Exiqon. Exiqon performed labeling, hybridization and data analysis after use of the miRCURY LNA™ microRNA Array (6th gen - hsa, mmu & rno). https://www.exiqon.com/ls/Documents/Scientific/miRCURY-LNA-microRNA-Array-6th-gen-hsa-mmu-rno-manual.pdf

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